Study of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Patients with Relapsed/Refractory Multiple Myeloma.

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2009-016138-29-PT
• Date of registration: 18/06/2013
• Prospective Registration: Yes
• Primary sponsor: Pharma Mar, S.A.
• Public title: Study of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Patients with Relapsed/Refractory Multiple Myeloma.
• Scientific title: Randomized, Multicenter, Open-label, Phase III Study of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Patients with Relapsed/Refractory Multiple Myeloma. - ADMYRE
• Date of first enrolment: 04/10/2013
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016138-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: yes; Other specify the comparator: Dexamethasone; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, Belgium, Czech Republic, France, Germany, Greece, Ireland, Italy, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Pharma Mar, S.A.

• Name: Clinical Trials
• Affiliation: Pharma Mar, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Concomitant diseases/conditions:
a) History or presence of angina, myocardial infarction, clinically relevant valvular heart disease, cardiac amyloidosis or congestive heart
failure within the last 12 months.
b) Symptomatic arrhythmia (excluding anemia-related sinusal tachycardia grade <= 2) or any arrhythmia requiring ongoing treatment,
and/or prolonged QT-QTc grade >= 2; or presence of unstable atrial fibrilation. Patients with stable atrial fibrillation on treatment are allowed provided they do not meet any other cardiac or prohibited drug exclusion criterion.
c) Active uncontrolled infection.
d) Morphological or cytological features of myelodysplasia and/or postchemotherapy aplasia on BM assessment.
e) Myopathy > grade 2 or any clinical situation that causes significant and persistent elevation of CPK (>2.5 x ULN in two different determinations performed one week apart).
f) Known human immunodeficiency virus (HIV) infection (HIV testing is not required unless infection is clinically suspected).
g) Known active hepatitis B or C virus (HBV or HCV) infection.
h) Limitation of the patient?s ability to comply with the treatment or follow-up requirements.
i) Any other major illness that, in the Investigator´s judgment, will substantially increase the risk associated with the patient´s
participation in this study.
j) Peripheral neuropathy > grade 2.
2. Women who are pregnant or breast feeding.
3. Concomitant medications that include corticosteroids, chemotherapy, or other therapy that is or may be active against MM, within two weeks prior to Cycle 1 Day 1. Concurrent corticosteroids are allowed, provided
they are administered at an equivalent prednisone dose of <= 10 mg daily, as premedication for blood products only.
4. Known history of peptic ulcer and/or major upper gastrointestinal bleeding episode occurring during last year before study entry and/or
related to prior steroid-based therapy.
5. Relevant history of mood-disturbances changes associated with previous steroid-based therapy.
6. Disease-related symptomatic hypercalcemia despite optimal medical therapy.
7. Known hypersensitivity to any involved study drug or any of its formulation components.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 138
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 112

Exclusion criteria:
1. Concomitant diseases/conditions:
a) History or presence of angina, myocardial infarction, clinically relevant valvular heart disease, cardiac amyloidosis or congestive heart failure within the last 12 months.
b) Symptomatic arrhythmia (excluding anemia-related sinusal tachycardia grade <= 2) or any arrhythmia requiring ongoing treatment, and/or prolonged QT-QTc grade >= 2; or presence of unstable atrial fibrilation. Patients with stable atrial fibrillation on treatment are allowed provided they do not meet any other cardiac or prohibited drug exclusion criterion.
c) Active uncontrolled infection.
d) Morphological or cytological features of myelodysplasia and/or post-chemotherapy aplasia on BM assessment.
e) Myopathy > grade 2 or any clinical situation that causes significant and persistent elevation of CPK (>2.5 x ULN in two different determinations performed one week apart).
f) Known human immunodeficiency virus (HIV) infection (HIV testing is not required unless infection is clinically suspected).
g) Known active hepatitis B or C virus (HBV or HCV) infection.
h) Limitation of the patient?s ability to comply with the treatment or follow-up requirements.
i) Any other major illness that, in the Investigator?s judgment, will substantially increase the risk associated with the patient?s participation in this study.
j) Peripheral neuropathy > grade 2.
2. Women who are pregnant or breast feeding.
3. Concomitant medications that include corticosteroids, chemotherapy, or other therapy that is or may be active against MM, within two weeks prior to Cycle 1 Day 1. Concurrent corticosteroids are allowed, provided they are administered at an equivalent prednisone dose of <= 10 mg daily, as premedication for blood products only.
4. Known history of peptic ulcer and/or major upper gastrointestinal bleeding episode occurring during last year before study entry and/or related to prior steroid-based therapy.
5. Relevant history of mood-disturbances changes associated with previous steroid-based therapy.
6. Disease-related symptomatic hypercalcemia despite optimal medical therapy.
7. Known hypersensitivity to any involved study drug or any of its formulation components.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsed/Refractory Multiple Myeloma
MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: APLIDIN (plitidepsin)
Product Code: Not applicable
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: plitidepsin
CAS Number: 137219-37-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: FORTECORTIN 4 mg Tabletten
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Primary Outcome(s)

Secondary Objective: To evaluate tumor response according to the International Myeloma Working Group (IMWG) criteria.
To assess duration of response (DR) and overall survival (OS).
To assess efficacy in patients who undergo crossover from dexamethasone alone to plitidepsin and dexamethasone combination.
To characterize and compare the safety profile on both arms in this population.
To characterize the pharmacokinetics (PK) and pharmacokinetic /pharmacodynamic (PK/PD) relationship.

Timepoint(s) of evaluation of this end point: Estimated average: 5 months. From randomization to the first evidence of progressive disease or death due to any cause

Main Objective: To compare the efficacy of plitidepsin in combination with dexamethasone vs. dexamethasone alone as measured by progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (MM).

Primary end point(s): PFS, according to IRC assessment, as per intention-to-treat (ITT) analysis.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Response rate: Every 4 weeks untill progression
Duration of Response: Estimated average: 3 months. From the date of first documentation of response to the date of disease
progression or death.
Overall Survival: Estimated average: 9 months. From randomization to the first evidence of progressive disease or death due to any cause

Secondary end point(s): Response rate
Duration of Response
Overall Survival

Secondary ID(s)

APL-C-001-09

2009-016138-29-FR

Source(s) of Monetary Support

Pharma Mar, S.A.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 18/11/2018
• Date Completed: 20/11/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-016138-29/results